Development of a receptor model for efficient in silico screening of HIV-1 integrase inhibitors

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2014 vol. 52 p. 82 - 82

ntegrase (IN) is a key viral enzyme for the replication of the type-1 human immunodeficiency virus (HIV-1), and as such constitutes a relevant therapeutic target for the development of anti-HIV agents. However,the lack of crystallographic data of HIV IN complexed with the corresponding viral DNA has historicallyhindered the application of modern structure-based drug design techniques to the discovery of newpotent IN inhibitors (INIs). Consequently, the development and validation of reliable HIV IN structuralmodels that may be useful for the screening of large databases of chemical compounds is of particularinterest. In this study, four HIV-1 IN homology models were evaluated respect to their capability to predictthe inhibition potency of a training set comprising 36 previously reported INIs with IC50 values in the lownanomolar to the high micromolar range. Also, 9 inactive structurally related compounds were includedin this trainin